Search PubMed⌕ Search

Biomedical subjects

L W Chang

Publications and source records attributed to L W Chang.

At least 73 records · Page 4Linked to original sources
PubMed1985

Early effects of trimethyltin on the dentate gyrus basket cells: a morphological study.

Electrophysiological evidence for reduction of recurrent inhibition in the dentate gyrus in animals exposed to trimethyltin (TMT) suggested alterations in the inhibitory neurons (basket cells) by TMT. The present study was designed to investigate the morphology of basket cells after TMT exposure. Long-Evans hooded rats were injected with TMT chloride in a dose of 6.0 mg/kg body weight (b.w.). Tissue samples from the dentate gyri were examined by both light and electron microscopy at 24 and 72 h after TMT exposure. Except for isolated basket cell damage at 72 h, no remarkable pathological changes were observed with light microscopy. Consistent with previous data, electron microscopy revealed that the basket cells of the dentate gyrus are large neurons situated just below the granule cell layer with characteristic large, infolded nuclei and intranuclear filamentous rods. Increased cytoplasmic density and degenerative changes of the Golgi complex were evident in the basket cells as early as 24 h after TMT exposure. By 72 h, neuronal vacuolation, accumulation of lysosomes, and occasional neuronal necrosis were observed. No significant pathological changes were found among the granule cells at this time. This report provides the first morphological evidence for early damage to the basket cells by TMT, which may account for the reduction of recurrent inhibition and hyperexcitability among the granule cells reported previously.

Animals↗
PubMed1985

Duration of maternally derived antibodies against equine influenza in newborn foals.

Serum antibody concentrations against influenza A-equi-1 virus and A-equi-2 virus were measured in a group of 18 foals from birth to 4 months of age. More than 50% of the foals were seronegative to A-equi-1 virus infection by 4 weeks of age, with titers of less than or equal to 1:16. For A-equi-2 virus, more than 50% of the foals were seronegative by 2 weeks of age, with titers of less than or equal to 1:8. Passively derived antibodies against influenza A-equi-1 virus and A-equi-2 virus in foals obtained from recently vaccinated mares and from mares not vaccinated within 6 months before foaling were low in titer. The duration of passively derived antibodies was also short-lived.

Animals↗
PubMed1984

Binding of chloroform to the cysteine of hemoglobin.

The products of the covalent binding of chloroform to rat hemoglobin during microsomal metabolism were isolated and identified by gas chromatography (GC) and mass spectroscopy (MS). After isolation by Proteinase K hydrolysis, amino acid analysis and cellulose thin-layer chromatography (TLC), the major product was identified by GC/MS as N-hydroxymethyl cysteine and a minor product as 2-hydroxythiazolidine-4-carboxylic acid. N-Hydroxymethyl cysteine is proposed to be formed during isolation from the 2-oxothiazolidine-4-carboxylic acid present in the intact hemoglobin.

Amino Acids↗
PubMed1984

Behavioral effects of trimethyltin in two strains of mice. I. Spontaneous motor activity.

Adult male mice (C57BL/6N and BALB/c) were administered single doses of trimethyltin X Cl (TMT) by the ip route. The effects of TMT administration were determined on lethality (3-6 mg/kg), spontaneous motor activity (SMA), and the physical appearance of the mice (0.3-3 mg/kg). The effects of TMT on lethality were strain dependent in that a single dose of 3 mg/kg, ip, produced approximately 35% lethality in the C57BL/6N strain during the first 72 hr following administration. Less than 15% lethality was observed at this dose in the BALB/c strain. In both strains, 3.5 mg/kg, ip, produced more than 70% lethality during the first 144 hr after administration. Higher doses produced proportionally greater lethality. The SMA of both strains was not affected significantly at doses below 1 mg/kg, ip. At 1 mg/kg a small decrease in activity was observed during the first 24 hr. At 3 mg/kg, SMA was initially decreased in both strains. However, the decrease was of smaller magnitude in the C57BL strain and was followed by a large increase in SMA which did not return to control levels for approximately 1 week. An increase in SMA was observed in the BALB/c strain on the fifth day following TMT but returned to control values by Day 6. At 3 mg/kg, ip, the C57BL mice were observed to have severe whole body tremors and were hypersensitive to external stimuli. The whole body tremor was not as marked in the BALB/c strain. Neuropathological studies on the treated mice indicated that the behavioral studies paralleled the pathology produced by TMT. These data confirm the initial observation of greater sensitivity of the mouse to toxic effects of TMT compared to the rat.

Animals↗
PubMed1984

Behavioral effects of trimethyltin in two strains of mice. II. Multiple fixed ratio, fixed interval.

Adult male C57BL/6N and BALB/c mice were trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of milk presentation. After performance had stabilized, each mouse received a single dose of trimethyltin X Cl (TMT) by ip administration. Three hours after administration, behavioral testing was started and continued at 24-hr intervals thereafter. The behavior of mice receiving 0.3 mg/kg was unaffected at 3, 27, and 51 hr after administration. Likewise, no effects were seen at 3 and 27 hr after 1 mg/kg. However, at 51 hr after administration there was a significant change in the temporal patterning of fixed-interval responding in the C57BL/6N strain, as shown by a decrease in the fixed-interval quarter-life. There was no significant change in the BALB/c strain at this dose. At 3 mg/kg the responding of both strains was greatly affected, and responding remained disrupted for at least 6 to 7 weeks. Neuropathological examination of the brains of both strains of mice showed no significant lesions (light microscopy) at 0.3 and 1 mg/kg. At 3 mg/kg, severe neuronal necrosis was observed in the fascia dentata region in both strains. Thus, in mice receiving TMT, the behavioral deficits were closely paralleled by the presence or absence of significant neuropathology.

Animals↗
PubMed1984

Neuropathology of trimethyltin intoxication. IV. Changes in the spinal cord.

Young C57BL/6N mice were injected (ip) with trimethyltin chloride at a dosage of 3.0 mg/kg body wt. Animals were sacrificed between 48 to 72 hr postinjection by means of intracardial perfusion of saline solution followed by 2.5% buffered glutaraldehyde. For light microscopy, the cords were further fixed in 10% buffered formalin and embedded in Paraplast. For electron microscopy, tissue samples were obtained from the cord levels at L1-L4, further fixed in glutaraldehyde and osmium tetroxide, and embedded in Epon. Chromatolytic and vacuolar changes involving neurons mainly in the medial and lateral motor nuclei of the anterior horns were observed. Electron microscopy revealed lysosomal accumulation and extensive dilatation of the cytoplasmic membrane systems (endoplasmic reticulum, Golgi complex). Large intraneuronal vacuoles were formed as a result of extensive intraneuronal edema. Progressive distention of the cytoplasmic membranes resulted in severe vacuolation, disintegration, and total breakdown of the neurons.

Animals↗
PubMed1984

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde.

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.

Air Pollutants, Occupational↗
PubMed1984

The potential oncogenic activity of influenza A virus in lungs of mice.

Adult male CD1 mice were inoculated with chicken egg-propagated influenza type A/PR8/34 virus. Fully developed pulmonary pneumonia was found 7 d after the infection. In addition to the pneumatic condition, pronounced thickening of the bronchiolar epithelium denoting hyperplastic and dysplastic transformation of the epithelial cells were also observed. By 11 d of the experiment, extensive papillomatous proliferation of the bronchiolar epithelial cells could be demonstrated. Furthermore, invasive growth of these epithelial cells through the basement membrane and muscularis layer into the alveolar tissues were evident. Such invasive transgression of transformed epithelial cells strongly suggested malignant growth of these cells. Detailed histopathological survey of all the virus-infected lungs revealed tumorous nodule formations in over 80% of the specimens examined. Our present investigation not only confirmed previous claims that cellular transformations (hyperplasia, metaplasia, dysplasia) can be induced with influenza type A virus but also for the first time successfully demonstrated invasive growth and tumorous formation in lungs of infected animals. Our study further reaffirms the oncogenic potential of influenza type A virus.

Animals↗
PubMed1984

Hippocampal lesions induced by trimethyltin in the neonatal rat brain.

The neuropathology of trimethyltin (TMT) chloride on neonatal rat hippocampus was investigated. It was found that the development of pathological lesions in the developing hippocampus is age-dependent and the most vulnerable age period was between postnatal days (PND) 9 and 15. TMT-treated animals appeared to be significantly stunned in growth. Brains of these animals were also markedly smaller than those of age-matched controls. Histopathology and electron microscopy examination of the hippocampus on PND 15, 21 and 24 from animals exposed to 6.0 mg TMT-Cl/kg b.w. on PND 11 revealed rapid destructions of the Ammon's horn. The granule cells of fascia dentata, despite some non-specific pathological changes (swelling, lysosomal accumulation), showed only minimal necrotic activity. Pyramidal neurons of the Ammon's horn, however, displayed extensive damage. Extensive neuronal edema, accumulation of lysosomes and myelinoid membranous bodies and cellular necrosis were observed as early as 4 days (PND 15) after exposure. By PND 24, total abolishment of the Ammon's horn occurred with extensive dystrophic calcification and astrocytic gliosis of the area.

Age Factors↗
PubMed1983

Corn oil-induced changes in the dorsal root ganglia of rats.

The effects of corn oil on rat dorsal root ganglia (DRG) were examined by both light and electron microscopy. Rats were fed corn oil via intubation 5 days per week for 7 weeks. No apparent morphological lesion was observed in the DRG by means of light microscopic examination. However, various cytological changes were revealed by electron microscopy. The most prominent change was the extensive and severe edematous condition in the interstitial space. After 7 weeks of treatment, the interstitial space between neurons and nerve fibers was distended by proteinaceous edematous fluid and collagen fibers. Distention of the intercellular space between the ganglion neurons and their surrounding satellite cell sheaths also occurred. Proliferation of the supporting cells, especially the satellite cells and Schwann cells, producing long and complex networks of cellular processes in the distended interstitial space was also evident. It is believed that chronic ingestion of corn oil by rats has an adverse effect on the endothelial system leading to an increased fluid permeability and edematous condition.

Animals↗
PubMed1983

Potentiation of Cd-induced pulmonary injury in alpha 1-antitrypsin suppressed rats.

The interrelationship of alpha 1-antitrypsin (alpha 1-AT) or serum trypsin inhibitor capacity (TIC) level and cadmium exposure in the induction of pulmonary lesions was investigated. Sprague-Dawley rats were exposed to CdCl2, galactosamine, or galactosamine + CdCl2 for 24 hr. Biochemical study indicated a 20% reduction of serum TIC in animals exposed to galactosamine. A marked, 50%, reduction of serum TIC was induced in animals exposed to galactosamine + CdCl2. Histopathological study revealed no major morphological lesions in lungs of animals exposed to either CdCl2 or galactosamine. However, extensive lesions, including polymorphonuclear leukocyte (PMN) infiltration, distortion and distention of the alveolar spaces, and massive hemorrhages were observed in the lungs of animals exposed to galactosamine + CdCl2. It is believed that cadmium can induce rapid lesions in the pulmonary tissues when the alpha 1-AT is significantly suppressed. The present investigation has provided direct evidence on the importance and interrelationship of cadmium and alpha 1-AT in pulmonary lesion development.

Animals↗
PubMed1983

Neuropathology of trimethyltin intoxication. III. Changes in the brain stem neurons.

Young adult BALB/c mice were administered trimethyltin chloride (TMT) at a dosage of 3.0 mg TMT/kg body wt. Animals displayed severe toxic signs (tremor and aggression) within 24 hr and were sacrificed at 48 and 72 hr postinjection. The brain stems of these animals were examined with light and electron microscopy. Degenerative and vacuolar changes were observed in many large brain stem neurons, especially those in the mesencephalic trigeminal nuclei. These neurons acquired a chromatolytic character with eccentric nuclei, loss of Nissl substance, and hyalinoid cytoplasm. Extensive vacuolation was also found in these nerve cells. Electron microscopy examination revealed progressive loss of the Nissl substance (rough endoplasmic reticulum) and distention of the cytoplasmic membranes (endoplasmic reticulum and Golgi complex). Severe distention of these membranes resulted in large membrane-limited vacuoles within these nerve cells. This intraneuronal vacuolation reflects an intracellular edema condition of these nerve cells and is potentially reversible. Mitochondrial damage in these neurons was only moderate. Further investigation is needed to elucidate the full toxic impact and pathogenetic mechanisms of TMT in the nervous system.

Animals↗
PubMed1983

Protective effects of selenium against methylmercury neurotoxicity: a morphological and biochemical study.

The protective effect of selenium (as sodium selenite) against methylmercury neurotoxicity was investigated morphologically and biochemically. Young adult Charles River rats were divided into 4 groups and were treated (i. p. injection) with methylmercury chloride (2 mg MeHg/kg b.w.), sodium selenite (2 mg Se/kg b.w.), both MeHg and Se, or with saline solution for 8 weeks. Four animals from each group were randomly selected for pathological investigation. These animals were sacrificed by intracardiac perfusion. The dorsal root ganglia (DRG) were dissected out for both light and electron microscopic examination. Six animals from each group were injected with 14 C-leucine 3 hours prior to sacrifice. The brains (cerebrum and cerebellum) of these animals were removed, weighed, homogenized and subjected to liquid scintillation analysis. Morphological investigation revealed extensive degenerations of the dorsal root fibers and destructions of neuronal Nissl substances in animals treated with MeHg alone. In MeHg/Se-treated animals, no neuronal change was observed and the nerve fiber damage was also significantly reduced. Proliferative thickenings of the myelin membrane, however, were observed in some dorsal root fibers. These proliferative membrane thickenings tend to protrude into the axonal compartment of the nerve fibers causing compression and shrinkage of the axons. It is believed that this proliferative, membraneous whirling phenomenon may represent a simultaneous destruction/repair condition of the myelin sheaths. Biochemical investigation also demonstrated a significant suppression of amino acid uptake (protein synthesis) in the CNS under the toxic influence of MeHg. However, such suppression effect was largely blocked or alleviated by selenium. Therefore, we have provided both morphological and biochemical evidences on the protective effect of selenium on methylmercury neurotoxicity.

Animals↗
PubMed1983

Developmental effects of trimethyltin intoxication in the neonatal mouse. I. Light microscopic studies.

The effects of trimethyltin (TMT) intoxication on the developing mouse brain were studied. BALB/c mice were injected intraperitoneally with 3.0 mg TMT/kg body weight on postnatal day 3. Animals were sacrificed at selected intervals to 30 days of age and their brains examined by light microscopy. Increased eosinophilia and granularity of hippocampal pyramidal neurons and neurons of the pyriform cortex were detected as early as 16 hours post-administration. Extensive degenerative and necrotic charges were observed 1 to 10 days post-administration, particularly in hippocampal region CA-3 of Ammon's horn. Cerebellar Purkinje and granule neurons, basal ganglia and cerebral cortex were involved to a lesser extent. Pathological changes of granule cells in the fascia dentata were much less extensive than reported in adult mice. Astrogliosis was occasionally pronounced. Distribution of lesions within the hippocampus indicate that acute neonatal TMT exposure results in a different regional pattern of injury than in acutely treated adult mice.

Animals↗
PubMed1982

Binding of chloroform to mouse and rat hemoglobin.

The covalent binding of chemical carcinogens and mutagens to hemoglobin has been proposed as a dose monitor for environmental exposure. The binding of chloroform to hemoglobin in rats was demonstrated to result from the formation of addition adducts to amino acids in the globin. The altered amino acids were isolated with an amino acid analyzer employing ion exchange chromatography. The covalent binding of orally-administered [14C]chloroform to rat hemoglobin reached a peak within 10 h. Afterwards, the amount of chloroform bound decreased slowly with half remaining at 7 weeks. The extent of chloroform binding was linearly dependent upon dose between 0.1 and 100 mumol/kg. Above 100 mumol/kg chloroform the binding to hemoglobin increased at a reduced rate. The extent of [14C]chloroform binding resulting from either 10 daily doses of 0.1 mumol/kg or a single 1.0 mumol/kg was similar. The binding to hemoglobin in three strains of mice and rats varied from 85 +/- 7 mumol/g Hb for Swiss (CFN) mice to 152 +/- 14 for Fisher-344 rats. We have demonstrated that the binding of chloroform to hemoglobin appears to have the following attributes of a dose monitor: (1) easily accessible from laboratory animals (and humans); (2) dose dependent; (3) stability, so that exposure can be determined weeks after it has ceased; (4) integration of low exposures which individually would be undetectable.

Amino Acids↗